CYP11B2

gene
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Also known as CYP11BLCPN2P-450C18P450aldoALDOS

Summary

CYP11B2 (cytochrome P450 family 11 subfamily B member 2, HGNC:2592) is a protein-coding gene on chromosome 8q24.3, encoding Cytochrome P450 11B2, mitochondrial (P19099). A cytochrome P450 monooxygenase that catalyzes the biosynthesis of aldosterone, the main mineralocorticoid in the human body responsible for salt and water homeostasis, thus involved in blood pressure regulation, arterial hypertension, and the development of heart failure.

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the mitochondrial inner membrane. The enzyme has steroid 18-hydroxylase activity to synthesize aldosterone and 18-oxocortisol as well as steroid 11 beta-hydroxylase activity. Mutations in this gene cause corticosterone methyl oxidase deficiency.

Source: NCBI Gene 1585 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): familial hyperreninemic hypoaldosteronism type 2 (Definitive, ClinGen) — +3 more curated relationships
  • GWAS associations: 16
  • Clinical variants (ClinVar): 658 total — 49 pathogenic, 43 likely-pathogenic
  • Phenotypes (HPO): 39
  • Druggable target: yes — 12 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_000498

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:2592
Approved symbolCYP11B2
Namecytochrome P450 family 11 subfamily B member 2
Location8q24.3
Locus typegene with protein product
StatusApproved
AliasesCYP11BL, CPN2, P-450C18, P450aldo, ALDOS
Ensembl geneENSG00000179142
Ensembl biotypeprotein_coding
OMIM124080
Entrez1585

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000323110, ENST00000945895, ENST00000945896

RefSeq mRNA: 1 — MANE Select: NM_000498 NM_000498

CCDS: CCDS6393

Canonical transcript exons

ENST00000323110 — 9 exons

ExonStartEnd
ENSE00001225434142912530142912727
ENSE00001301821142917602142917843
ENSE00001387551142910559142912093
ENSE00001638180142914705142914908
ENSE00001649336142915046142915245
ENSE00001690999142912807142912885
ENSE00001738697142917059142917214
ENSE00001785304142913285142913451
ENSE00001786255142914264142914418

Expression profiles

Bgee: expression breadth broad, 30 present calls, max score 92.72.

Top tissues by expression

244 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
right adrenal gland cortexUBERON:003582792.72gold quality
right adrenal glandUBERON:000123392.16gold quality
left adrenal glandUBERON:000123490.22gold quality
adrenal cortexUBERON:000123588.61gold quality
adrenal glandUBERON:000236987.86gold quality
left adrenal gland cortexUBERON:003582586.98gold quality
gluteal muscleUBERON:000200084.79gold quality
parotid glandUBERON:000183184.72gold quality
heart right ventricleUBERON:000208083.39gold quality
triceps brachiiUBERON:000150982.10gold quality
inferior olivary complexUBERON:000212779.43gold quality
tongue squamous epitheliumUBERON:000691978.81gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047377.28silver quality
choroid plexus epitheliumUBERON:000391176.98gold quality
olfactory bulbUBERON:000226476.83gold quality
vena cavaUBERON:000408776.78gold quality
dorsal motor nucleus of vagus nerveUBERON:000287076.63gold quality
cervix squamous epitheliumUBERON:000692276.35gold quality
type B pancreatic cellCL:000016975.60gold quality
nasal cavity epitheliumUBERON:000538475.54gold quality
skeletal muscle tissue of rectus abdominisUBERON:000451174.55gold quality
skeletal muscle tissue of biceps brachiiUBERON:000450274.49gold quality
lateral nuclear group of thalamusUBERON:000273673.58gold quality
cerebellar vermisUBERON:000472073.25gold quality
body of tongueUBERON:001187673.10gold quality
biceps brachiiUBERON:000150772.77gold quality
Brodmann (1909) area 46UBERON:000648371.94gold quality
endothelial cellCL:000011571.88gold quality
subthalamic nucleusUBERON:000190671.75gold quality
medulla oblongataUBERON:000189671.50gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

ExperimentMarker?Max mean expression
E-ANND-3no0.98

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): APEX1, AR, ATF1, ATF2, C1QTNF1, CREB1, DMRT1, FOXL2, JUNB, NR2F1, NR4A1, NR4A2, NR5A1, REST, TCF3

miRNA regulators (miRDB)

41 targeting CYP11B2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4692100.0067.322066
HSA-MIR-451499.9967.101870
HSA-MIR-512-3P99.9767.351049
HSA-MIR-448799.9664.581252
HSA-MIR-4731-5P99.8967.232537
HSA-MIR-7845-5P99.8864.88771
HSA-MIR-549A-3P99.5468.17825
HSA-MIR-671-5P99.5267.111277
HSA-MIR-608099.4369.43373
HSA-MIR-94099.3766.142064
HSA-MIR-6893-5P99.3166.252119
HSA-MIR-6808-5P99.3166.232150
HSA-MIR-6731-5P99.2867.422375
HSA-MIR-808599.2867.562362
HSA-MIR-450599.2767.812678
HSA-MIR-6878-3P99.2464.23920
HSA-MIR-578799.2267.862628
HSA-MIR-6852-5P99.1766.692073
HSA-MIR-425499.1165.151315
HSA-MIR-485-5P99.1064.781889
HSA-MIR-6884-5P99.1064.501987
HSA-MIR-2467-3P98.6567.181969
HSA-MIR-4700-5P98.6367.431915
HSA-MIR-4722-5P98.4666.341611
HSA-MIR-5008-5P98.4265.871019
HSA-MIR-211-3P98.1466.771052
HSA-MIR-18B-3P98.0565.55595
HSA-MIR-607298.0066.47804
HSA-MIR-6765-3P97.8364.591165
HSA-MIR-392197.8167.451431

Literature-anchored findings (GeneRIF, showing 40)

  • The unmodified mitochondrial localization signal of human CYP11B2 is functional when expressed in fission yeast, and overexpression of the gene significantly enhances steroid hydroxylase activity of CYP11B2-expressing fission yeast cells. (PMID:11841224)
  • Substrate recognition and conversion are attributed to the N-terminal part of human CYP11B2. (PMID:11856349)
  • role in familial hyperaldosteronism (PMID:11903322)
  • Differential regulation of aldosterone synthase and 11beta-hydroxylase transcription by steroidogenic factor-1 (PMID:11932209)
  • investigate the relationship of gene polymorphism of angiotension converting enzyme (ACE), aldosterone synthase (CYP11B2) with essential hypertension (EH) and left ventricular hypertrophy (LVH) in hypertensive patients (PMID:12133420)
  • Expression of aldosterone synthase gene in failing human heart (PMID:12161536)
  • Carotid and femoral intima-media thickness were assessed in subjects genotyped for the presence of the ACE D, aldosterone synthase -344T and alpha-adducin 460Trp alleles. (PMID:12172317)
  • CaMKI is involved in angiotensin II and K(+) stimulation of CYP11B2 transcription and the capacity of the adrenal to produce aldosterone (PMID:12193581)
  • Inter-individual variation of blood pressure and plasma aldosterone is affected by the interaction of C(-344)T polymorphism and ageing. (PMID:12195120)
  • Variation in locus contributes to hypertension in subjects with a raised aldosterone-to-renin ratio (PMID:12213905)
  • CT genotype of CYP11B2 gene may be one of factors responsible for the pathogenesis of hypertrophic cardiomyopathy HCM in a proportion of patients. (PMID:12376254)
  • The study of association of CYP11B2 polymorphism with hypertension in Russian patients in Bashkorstan (PMID:12391843)
  • Contrasting associations between these variants and essential hypertension do not necessarily exclude the possibility that other, as yet undefined, variants of the aldosterone synthase gene could be linked with hypertension in black people. (PMID:12544440)
  • Genetic variation in or near the CYP11B2 gene is a possible genetic marker for the progression of renal dysfunction in females with IgA nephropathy, but not in males (PMID:12746403)
  • Linear modeling of postural changes in renin and aldosterone showed a maximal achievable aldosterone increase of 110 pmol/liter with no mutated haplotype and 500 pmol/liter with two mutated haplotypes. Molecular basis for aldosterone production. (PMID:12788845)
  • Exon 3 mutation (C554T, leading to amino acid T185I) and exon 9 mutation (A1492G, leading to T498A)localize to beta 3-sheet in cytochrome P450 enzyme structure. Aldosterone synthase catalyzes oxygenation of the C(18) carbon of steroid substrates. (PMID:12788848)
  • The T-344C and A6547G, but not the T4986C, variants of the aldosterone synthase gene are associated with HT in females of the Anglo-Celtic population studied. (PMID:12817181)
  • A variant within the CYP11B2 locus has a clinically important impact on the severity of SBP changes in individuals with newly diagnosed hypertension who are of African ethnicity. (PMID:14643573)
  • Our data suggest that -344C/T polymorphism in the promoter region of the aldosterone synthase gene affects left ventricular mass and thickness in essential hypertension, independent of adrenal aldosterone. (PMID:14736447)
  • -344C/T polymorphism in CYP11B2 was considered an independent genetic factor possibly associated with hypertension or atherosclerotic diseases in the Japanese population. (PMID:15055249)
  • identified two new variants in CYP11B2, a C/T single nucleotide exchange located in the first intron and a double nucleotide exchange at the 3’-splice site of exon 8 (PMID:15062555)
  • The ACE I/D, alpha-adducin Gly460Trp and aldosterone synthase -344C/T polymorphisms interact to influence systolic blood pressure in Chinese, suggesting that these genes might indeed predispose to hypertension (PMID:15097233)
  • Aldosterone synthase genotype is unrelated to overall coronary artery disease events risk in male patients. (PMID:15135254)
  • TT genotype of T-344C polymorphism of aldosterone synthase gene was associated with significantly higher levels of plasma renin in normotensive men (PMID:15223724)
  • CYP11B2 C-344T and AT1R A1166C polymorphisms affect the autonomic modulation of heart rate, but these genetic effects depend on sodium excretion. (PMID:15238568)
  • In multi-ethnic population, C-344T CYP1B2 polymorphism is associated with blood pressure, plasma aldosterone levels and aldosterone-to-renin ratio. Significant differences in allele frequencies between groups. Ethnicity does not explain results. (PMID:15361760)
  • Renal function in relation to ALDOS was studied in a Han population. (PMID:15378162)
  • The results suggest that -344T/C polymorphism of CYP11B2 gene may be associated with low-renin essential hypertension in the Han nationality in Shandong province. (PMID:15505931)
  • Molecular variant in CYP11B2 is in linkage disequilibrium (LD) with a key quantitative trait in CYP11B1. (PMID:15507509)
  • Linkage disequilibrium between causative CYP11B1 variants and CYP11B2 polymorphisms account for urinary 11-deoxycortisol excretion. (PMID:15522937)
  • may be polymorphic among mult=ethnic groups as a risk factor for hypertension (PMID:15545843)
  • Aldo deficiency due to a compromised methyl oxidase step of Aldo synthesis favors extracellular volume depletion, and may account for an increased risk of placental hypoperfusion and consecutive development of preeclampsia (PMID:15569322)
  • data support a physiological role of Ubc9 and PIAS1 as transcriptional coactivators in COUP-TFI-mediated CYP11B2 transcription (PMID:15611122)
  • The CYP11B2 C-344T polymorphism affects arterial stiffness. However, sodium intake seems to modulate this genetic effect. (PMID:15614025)
  • The correlation of the intron-2 conversion allele with high systolic blood pressure and plasma renin ratio associates it with hypertension. (PMID:15643128)
  • Inactivating mutations cause aldosterone synthase deficiency. (PMID:15699546)
  • The -344CC or intron 2 conversion (-/-) genotype in CYP11B2 may be a risk factor for developing sodium-sensitive cardiac hypertrophy. (PMID:15894890)
  • aldosterone synthase gene polymorphism (ASGP) CYP11B2 influences the age-related changes in blood pressure (BP) and arterial stiffness in hypertensive subjects (PMID:15894891)
  • Subjects with the combination of ACE DD and CYP11B2 CC genotypes might have a better blood pressure response to hydrochlorothiazide than the other genotypic combinations of these 2 genes. (PMID:16080804)
  • The CYP11B-344C/T polymorphism is associated with small artery compliance, and TT genotype subjects are susceptible to abnormality of small arterial compliance. (PMID:16080805)

Cross-species orthologs

0 orthologs

Paralogs (2): CYP11A1 (ENSG00000140459), CYP11B1 (ENSG00000160882)

Protein

Protein identifiers

Cytochrome P450 11B2, mitochondrialP19099 (reviewed: P19099)

Alternative names: Aldosterone synthase, Aldosterone-synthesizing enzyme, CYPXIB2, Corticosterone 18-monooxygenase, CYP11B2, Cytochrome P-450Aldo, Cytochrome P-450C18, Steroid 11-beta-hydroxylase, CYP11B2, Steroid 18-hydroxylase

All UniProt accessions (1): P19099

UniProt curated annotations — full annotation on UniProt →

Function. A cytochrome P450 monooxygenase that catalyzes the biosynthesis of aldosterone, the main mineralocorticoid in the human body responsible for salt and water homeostasis, thus involved in blood pressure regulation, arterial hypertension, and the development of heart failure. Catalyzes three sequential oxidative reactions of 11-deoxycorticosterone (21-hydroxyprogesterone), namely 11-beta hydroxylation, followed by two successive oxidations at C18 yielding 18-hydroxy and then 18-oxo intermediates (that would not leave the enzyme active site during the consecutive hydroxylation reactions), ending with the formation of aldosterone. Can also produce 18-hydroxycortisol and 18-oxocortisol, derived from successive oxidations of cortisol at C18, normally found at very low levels, but significantly increased in primary aldosteronism, the most common form of secondary hypertension. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate and reducing the second into a water molecule. Two electrons are provided by NADPH via a two-protein mitochondrial transfer system comprising flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and nonheme iron-sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin). Could also be involved in the androgen metabolic pathway.

Subcellular location. Mitochondrion inner membrane.

Tissue specificity. Expressed sporadically in the zona glomerulosa (zG) of the adrenal cortex (conventional zonation), as well as in aldosterone-producing cell clusters (APCCs) composed of morphological zG cells in contact with the capsule (variegated zonation).

Disease relevance. Corticosterone methyloxidase 1 deficiency (CMO-1 deficiency) [MIM:203400] Autosomal recessive disorder of aldosterone biosynthesis. There are two biochemically different forms of selective aldosterone deficiency be termed corticosterone methyloxidase (CMO) deficiency type 1 and type 2. In CMO-1 deficiency, aldosterone is undetectable in plasma, while its immediate precursor, 18-hydroxycorticosterone, is low or normal. The disease is caused by variants affecting the gene represented in this entry. Corticosterone methyloxidase 2 deficiency (CMO-2 deficiency) [MIM:610600] Autosomal recessive disorder of aldosterone biosynthesis. In CMO-2 deficiency, aldosterone can be low or normal, but at the expense of increased secretion of 18-hydroxycorticosterone. Consequently, patients have a greatly increased ratio of 18-hydroxycorticosterone to aldosterone and a low ratio of corticosterone to 18-hydroxycorticosterone in serum. The disease is caused by variants affecting the gene represented in this entry.

Induction. Expression is induced by angiotensin II, potassium (K+), and also by cAMP.

Pathway. Steroid biosynthesis.

Miscellaneous. Expressed in aldosterone-secreting tumors and in adrenal glands of patients with idiopathic hyperaldosteronism.

Similarity. Belongs to the cytochrome P450 family.

RefSeq proteins (1): NP_000489* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR001128Cyt_P450Family
IPR002399Cyt_P450_mitochondrialFamily
IPR017972Cyt_P450_CSConserved_site
IPR036396Cyt_P450_sfHomologous_superfamily
IPR050479CYP11_CYP27_familiesFamily

Pfam: PF00067

Enzyme classification (BRENDA):

  • EC 1.14.15.4 — steroid 11beta-monooxygenase (BRENDA: 16 organisms, 122 substrates, 309 inhibitors, 38 Km, 19 kcat entries)
  • EC 1.14.15.5 — corticosterone 18-monooxygenase (BRENDA: 5 organisms, 15 substrates, 98 inhibitors, 3 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

SubstrateKm (mM)Measurements
11-DEOXYCORTICOSTERONE0.0008–0.1815
11-DEOXYCORTISOL0.0084–0.3386
CORTICOSTERONE0.0059–0.0874
ADRENAL FERREDOXIN0.002–0.00242
DEOXYCORTICOSTERONE0.006–0.022
4-ANDROSTENE-3,17-DIONE0.0131
CORTICOSTERONE0.0281

Catalyzed reactions (Rhea), 8 shown:

  • corticosterone + 2 reduced [adrenodoxin] + O2 + 2 H(+) = 18-hydroxycorticosterone + 2 oxidized [adrenodoxin] + H2O (RHEA:11872)
  • a steroid + 2 reduced [adrenodoxin] + O2 + 2 H(+) = an 11beta-hydroxysteroid + 2 oxidized [adrenodoxin] + H2O (RHEA:15629)
  • 11-deoxycortisol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = cortisol + 2 oxidized [adrenodoxin] + H2O (RHEA:46100)
  • 21-hydroxyprogesterone + 2 reduced [adrenodoxin] + O2 + 2 H(+) = corticosterone + 2 oxidized [adrenodoxin] + H2O (RHEA:46104)
  • 18-hydroxycorticosterone + 2 reduced [adrenodoxin] + O2 + 2 H(+) = aldosterone + 2 oxidized [adrenodoxin] + 2 H2O (RHEA:50792)
  • cortisol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = 18-hydroxycortisol + 2 oxidized [adrenodoxin] + H2O (RHEA:76019)
  • 18-hydroxycortisol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = 18-oxocortisol + 2 oxidized [adrenodoxin] + 2 H2O (RHEA:76023)
  • 21-hydroxyprogesterone + 2 reduced [adrenodoxin] + O2 + 2 H(+) = 18-hydroxy-11-deoxycorticosterone + 2 oxidized [adrenodoxin] + H2O (RHEA:76151)

UniProt features (70 total): helix 24, sequence variant 18, strand 13, sequence conflict 7, mutagenesis site 3, binding site 2, transit peptide 1, chain 1, turn 1

Structure

Experimental structures (PDB)

7 structures.

PDBMethodResolution (Å)
4DVQX-RAY DIFFRACTION2.49
4FDHX-RAY DIFFRACTION2.71
6XZ9X-RAY DIFFRACTION2.77
7M8IX-RAY DIFFRACTION2.94
6XZ8X-RAY DIFFRACTION3
7M8VX-RAY DIFFRACTION3.08
4ZGXX-RAY DIFFRACTION3.2

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P19099-F190.100.74

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (2): 381; 450 (axial binding residue)

Mutagenesis-validated functional residues (3):

PositionPhenotype
112increases 11-beta- and 18-hydroxylase activities toward 11-deoxycorticosterone; increases 11-beta-hydroxylase activity t
147increases 11-beta-hydroxylase activity toward 11-deoxycorticosterone and 11-deoxycortisol.
152no significant effect on hydroxylase activities toward 11-deoxycorticosterone and 11-deoxycortisol.

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

IDPathway
R-HSA-193993Mineralocorticoid biosynthesis
R-HSA-194002Glucocorticoid biosynthesis
R-HSA-211976Endogenous sterols
R-HSA-5579009Defective CYP11B2 causes CMO-1 deficiency
R-HSA-1430728Metabolism
R-HSA-1643685Disease
R-HSA-196071Metabolism of steroid hormones
R-HSA-211859Biological oxidations
R-HSA-211897Cytochrome P450 - arranged by substrate type
R-HSA-211945Phase I - Functionalization of compounds
R-HSA-556833Metabolism of lipids
R-HSA-5579029Metabolic disorders of biological oxidation enzymes
R-HSA-5668914Diseases of metabolism
R-HSA-8957322Metabolism of steroids

MSigDB gene sets: 309 (showing top): MODULE_93, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_BIOLOGICAL_OXIDATIONS, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GNF2_GSTM1, PEREZ_TP63_TARGETS, GOBP_GLUCOCORTICOID_METABOLIC_PROCESS, GOBP_RENAL_SYSTEM_PROCESS_INVOLVED_IN_REGULATION_OF_BLOOD_VOLUME, GNF2_HPN, GOBP_C21_STEROID_HORMONE_METABOLIC_PROCESS, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE, GOBP_REGULATION_OF_HORMONE_LEVELS

GO Biological Process (19): regulation of blood volume by renal aldosterone (GO:0002017), renal water homeostasis (GO:0003091), C21-steroid hormone biosynthetic process (GO:0006700), glucocorticoid biosynthetic process (GO:0006704), mineralocorticoid biosynthetic process (GO:0006705), cholesterol metabolic process (GO:0008203), sterol metabolic process (GO:0016125), aldosterone biosynthetic process (GO:0032342), cellular response to hormone stimulus (GO:0032870), cortisol metabolic process (GO:0034650), cortisol biosynthetic process (GO:0034651), cellular response to potassium ion (GO:0035865), potassium ion homeostasis (GO:0055075), sodium ion homeostasis (GO:0055078), cellular response to peptide hormone stimulus (GO:0071375), alcohol metabolic process (GO:0006066), lipid metabolic process (GO:0006629), steroid biosynthetic process (GO:0006694), steroid metabolic process (GO:0008202)

GO Molecular Function (9): steroid 11-beta-monooxygenase activity (GO:0004507), iron ion binding (GO:0005506), steroid hydroxylase activity (GO:0008395), heme binding (GO:0020037), corticosterone 18-monooxygenase activity (GO:0047783), monooxygenase activity (GO:0004497), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705), metal ion binding (GO:0046872)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-10 pathways:

CategoryPathways
Metabolism of steroid hormones2
Metabolism2
Cytochrome P450 - arranged by substrate type1
Metabolic disorders of biological oxidation enzymes1
Metabolism of steroids1
Phase I - Functionalization of compounds1
Biological oxidations1
Diseases of metabolism1
Disease1
Metabolism of lipids1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
steroid hormone biosynthetic process3
hormone biosynthetic process2
glucocorticoid metabolic process2
steroid metabolic process2
primary alcohol biosynthetic process2
ketone biosynthetic process2
olefinic compound biosynthetic process2
monoatomic cation homeostasis2
inorganic ion homeostasis2
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced iron-sulfur protein as one donor, and incorporation of one atom of oxygen2
oxidoreductase activity2
regulation of systemic arterial blood pressure by hormone1
positive regulation of systemic arterial blood pressure1
renal system process1
multicellular organismal-level water homeostasis1
C21-steroid hormone metabolic process1
mineralocorticoid metabolic process1
sterol metabolic process1
secondary alcohol metabolic process1
C21-steroid hormone biosynthetic process1
mineralocorticoid biosynthetic process1
aldosterone metabolic process1
aldehyde biosynthetic process1
response to hormone1
cellular response to chemical stimulus1
cellular response to endogenous stimulus1
primary alcohol metabolic process1
ketone metabolic process1
olefinic compound metabolic process1
tertiary alcohol metabolic process1
glucocorticoid biosynthetic process1
cortisol metabolic process1
tertiary alcohol biosynthetic process1
response to potassium ion1
cellular response to metal ion1
cellular response to hormone stimulus1
response to peptide hormone1
cellular response to nitrogen compound1
cellular response to oxygen-containing compound1
small molecule metabolic process1

Protein interactions and networks

STRING

1708 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
CYP11B2STARP49675922
CYP11B2RENP00797912
CYP11B2HSD11B2P80365901
CYP11B2AGTP01019897
CYP11B2AGTR1P30556871
CYP11B2ACEP12821864
CYP11B2MC2RQ01718842
CYP11B2NR5A1Q13285829
CYP11B2POMCP01189818
CYP11B2FDX1P10109812
CYP11B2KCNJ5P48544812
CYP11B2HSD3B2P26439794
CYP11B2NR3C2P08235792
CYP11B2ATP2B3Q16720763
CYP11B2NR0B1P51843757

IntAct

0 interactions, top by confidence:

BioGRID (10): CYP11B2 (Negative Genetic), HMGA1 (Negative Genetic), SSTR5 (Negative Genetic), MAP3K10 (Negative Genetic), PIM1 (Negative Genetic), CYP11B2 (Negative Genetic), CYP11B2 (Affinity Capture-MS), CYP11B2 (Affinity Capture-Western), TRIM2 (Affinity Capture-Western), CYP11B2 (Co-crystal Structure)

ESM2 similar proteins: O15528, O35074, O46515, O77809, O77810, P00187, P00189, P05108, P05177, P10611, P10612, P14137, P14579, P14580, P14581, P15150, P15393, P15538, P15539, P17177, P17178, P19099, P30099, P30100, P51663, P79153, P79202, P97720, Q02318, Q02928, Q07217, Q16647, Q28827, Q29527, Q29552, Q29626, Q2XV99, Q4H4C3, Q5KQT6, Q5TCH4

Diamond homologs: A0A068Q5V6, A0A068Q605, A0A068Q7V0, A0A0C5QRZ2, A0A0D9MRV9, A0A0N7F297, A0A1B4XBH0, A0A1B4XBH8, A0A1D6F9Y9, A0A1D6HSP4, A0A1W5T1Y6, A0A2H5AIX6, A0A2K9RG08, A0A3Q9R4N5, A0A4D6Q414, A0A4D6Q415, A0A517FNC5, A0A8K1AW54, A2QBE8, A6YIH8, B1GVX3, B8NHD9, B8NHY4, C9K202, D1MX85, E9KMQ3, E9Q816, F2K081, F4JW83, G3XSI3, G4N2X2, G5EJN7, H2DH18, H2DH24, L0N063, L7HT17, M1KVN4, M1KXD0, O13345, O22203

SIGNOR signaling

9 interactions.

AEffectBMechanism
APEX1“down-regulates quantity by repression”CYP11B2“transcriptional regulation”
NR5A1“down-regulates quantity by repression”CYP11B2“transcriptional regulation”
CYP11B2“up-regulates quantity”cortisol“chemical modification”
CYP11B2“down-regulates quantity”11-deoxycortisol“chemical modification”
CYP11B2“up-regulates quantity”corticosterone“chemical modification”
CYP11B2“down-regulates quantity”11-deoxycorticosterone“chemical modification”
CYP11B2“up-regulates quantity”18-hydroxycorticosterone“chemical modification”
CYP11B2“up-regulates quantity”aldosterone“chemical modification”
metyrapone“down-regulates activity”CYP11B2“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

658 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic49
Likely pathogenic43
Uncertain significance162
Likely benign334
Benign24

Top pathogenic / likely-pathogenic (30)

Variant IDHGVSClassification
1071836NM_000498.3(CYP11B2):c.342_343dup (p.Pro115fs)Pathogenic
1073733NM_000498.3(CYP11B2):c.1276C>T (p.Gln426Ter)Pathogenic
1074429NC_000008.10:g.(?143998465)(143999600_?)delPathogenic
1374879NM_000498.3(CYP11B2):c.553del (p.Thr185fs)Pathogenic
1387027NM_000498.3(CYP11B2):c.595+1delPathogenic
1414779NM_000498.3(CYP11B2):c.1034_1047del (p.Leu345fs)Pathogenic
1416764NM_000498.3(CYP11B2):c.1066C>T (p.Gln356Ter)Pathogenic
1455200NM_000498.3(CYP11B2):c.531del (p.Gln178fs)Pathogenic
1458193NM_000498.3(CYP11B2):c.892G>T (p.Glu298Ter)Pathogenic
1459295NM_000498.3(CYP11B2):c.217C>T (p.Gln73Ter)Pathogenic
16878NM_000498.3(CYP11B2):c.104_109delinsG (p.Val35fs)Pathogenic
16881NM_000498.3(CYP11B2):c.554C>T (p.Thr185Ile)Pathogenic
16884CYP11B2, IVS2 CONVERSIONPathogenic
2027037NM_000498.3(CYP11B2):c.916dup (p.Ala306fs)Pathogenic
2031382NM_000498.3(CYP11B2):c.845del (p.Arg282fs)Pathogenic
2097019NM_000498.3(CYP11B2):c.1084del (p.Leu362fs)Pathogenic
2098081NM_000498.3(CYP11B2):c.895del (p.Leu299fs)Pathogenic
2109017NM_000498.3(CYP11B2):c.240-1G>TPathogenic
2119763NM_000498.3(CYP11B2):c.1247T>A (p.Leu416Ter)Pathogenic
2136711NM_000498.3(CYP11B2):c.788T>A (p.Ile263Asn)Pathogenic
2136713NM_000498.3(CYP11B2):c.508C>T (p.Gln170Ter)Pathogenic
2423179NC_000008.10:g.(?143993936)(143994311_?)delPathogenic
2674683NM_000498.3(CYP11B2):c.546dup (p.Ser183fs)Pathogenic
2674686NM_000498.3(CYP11B2):c.793C>T (p.Gln265Ter)Pathogenic
2674688NM_000498.3(CYP11B2):c.954G>C (p.Thr318=)Pathogenic
2674696NM_000498.3(CYP11B2):c.1471C>T (p.Pro491Ser)Pathogenic
2697591NM_000498.3(CYP11B2):c.594A>T (p.Glu198Asp)Pathogenic
2702769NM_000498.3(CYP11B2):c.499del (p.Asp167fs)Pathogenic
2703927NM_000498.3(CYP11B2):c.1140del (p.Leu382fs)Pathogenic
2704824NM_000498.3(CYP11B2):c.180_184del (p.Tyr61fs)Pathogenic

SpliceAI

1591 predictions. Top by Δscore:

VariantEffectΔscore
8:142912528:A:ACdonor_gain1.0000
8:142912529:C:CCdonor_gain1.0000
8:142914276:C:CAdonor_gain1.0000
8:142914416:CAC:Cacceptor_gain1.0000
8:142914419:C:CCacceptor_gain1.0000
8:142914419:CT:Cacceptor_loss1.0000
8:142914424:C:CTacceptor_gain1.0000
8:142914424:C:Tacceptor_gain1.0000
8:142914704:CCGTA:Cdonor_gain1.0000
8:142914708:A:ACdonor_gain1.0000
8:142914709:C:CCdonor_gain1.0000
8:142915041:CACA:Cdonor_loss1.0000
8:142915042:ACAC:Adonor_loss1.0000
8:142915044:ACC:Adonor_loss1.0000
8:142915045:C:Adonor_loss1.0000
8:142915045:CCTT:Cdonor_gain1.0000
8:142915081:T:TAdonor_gain1.0000
8:142915241:CATTC:Cacceptor_gain1.0000
8:142915242:ATTC:Aacceptor_gain1.0000
8:142915243:TTC:Tacceptor_gain1.0000
8:142915243:TTCC:Tacceptor_loss1.0000
8:142915244:TC:Tacceptor_gain1.0000
8:142915245:CC:Cacceptor_gain1.0000
8:142915246:C:CAacceptor_loss1.0000
8:142915246:C:CCacceptor_gain1.0000
8:142915247:T:Gacceptor_loss1.0000
8:142917057:A:ACdonor_gain1.0000
8:142917058:C:CCdonor_gain1.0000
8:142917058:CAA:Cdonor_gain1.0000
8:142917123:T:TAdonor_gain1.0000

AlphaMissense

3288 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
8:142912599:A:CF443L0.993
8:142912599:A:TF443L0.993
8:142912601:A:GF443L0.993
8:142914904:G:CS200R0.990
8:142914904:G:TS200R0.990
8:142914906:T:GS200R0.990
8:142915230:C:AW137C0.990
8:142915230:C:GW137C0.990
8:142915232:A:GW137R0.990
8:142915232:A:TW137R0.990
8:142914273:G:CS315R0.989
8:142914273:G:TS315R0.989
8:142914275:T:GS315R0.989
8:142913374:G:CS344R0.987
8:142913374:G:TS344R0.987
8:142913376:T:GS344R0.987
8:142913294:T:AE371V0.985
8:142915219:C:GR141P0.985
8:142912578:G:CC450W0.984
8:142917108:A:GW116R0.984
8:142917108:A:TW116R0.984
8:142914726:A:GW260R0.982
8:142914726:A:TW260R0.982
8:142911996:A:GF499S0.981
8:142912570:C:GR453P0.981
8:142912580:A:GC450R0.981
8:142914286:A:GL311P0.981
8:142912586:G:TR448S0.979
8:142913295:C:TE371K0.978
8:142913414:G:TA331D0.978

dbSNP variants (sampled 300 via entrez): RS1000182985 (8:142919583 TTTA>T), RS1000921788 (8:142913188 G>A), RS1001157479 (8:142913564 A>C), RS1001183450 (8:142918518 C>T), RS1002584292 (8:142916815 C>T), RS1002643099 (8:142916630 C>G,T), RS1002764645 (8:142911426 G>A,C,T), RS1002935857 (8:142911207 A>G), RS1003528368 (8:142919753 A>G), RS1004313400 (8:142918871 C>T), RS1005277521 (8:142910633 C>A,T), RS1005726427 (8:142912320 C>G,T), RS1005931936 (8:142916389 C>A,G), RS1006012671 (8:142911126 A>G), RS1006065351 (8:142910921 G>A)

Disease associations

OMIM: gene MIM:124080 | disease phenotypes: MIM:203400, MIM:610600, MIM:103900, MIM:606984

GenCC curated gene-disease

DiseaseClassificationInheritance
corticosterone methyloxidase type 2 deficiencyStrongAutosomal recessive
corticosterone methyloxidase type 1 deficiencyModerateAutosomal recessive
familial hypoaldosteronismSupportiveAutosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

DiseaseClassificationInheritance
familial hyperreninemic hypoaldosteronism type 2DefinitiveAR

Mondo (6): corticosterone methyloxidase type 1 deficiency (MONDO:0008751), corticosterone methyloxidase type 2 deficiency (MONDO:0012524), glucocorticoid-remediable aldosteronism (MONDO:0007080), early-onset familial hypoaldosteronism (MONDO:0035320), familial hypoaldosteronism (MONDO:0018541), familial hyperreninemic hypoaldosteronism type 2 (MONDO:0011754)

Orphanet (4): Familial hypoaldosteronism (Orphanet:427), Familial hyperaldosteronism type I (Orphanet:403), Early-onset familial hypoaldosteronism (Orphanet:556030), OBSOLETE: Familial hyperreninemic hypoaldosteronism type 2 (Orphanet:99764)

HPO phenotypes

39 total (30 of 39 shown, HPO-id order):

HPOTerm
HP:0000007Autosomal recessive inheritance
HP:0000127Renal salt wasting
HP:0000360Tinnitus
HP:0000421Epistaxis
HP:0000811Abnormal external genitalia morphology
HP:0000822Hypertension
HP:0000848Increased circulating renin concentration
HP:0001278Orthostatic hypotension
HP:0001290Generalized hypotonia
HP:0001324Muscle weakness
HP:0001508Failure to thrive
HP:0001510Growth delay
HP:0001944Dehydration
HP:0001954Recurrent fever
HP:0001959Polydipsia
HP:0002013Vomiting
HP:0002018Nausea
HP:0002153Hyperkalemia
HP:0002170Intracranial hemorrhage
HP:0002315Headache
HP:0002615Hypotension
HP:0002900Hypokalemia
HP:0002902Hyponatremia
HP:0003623Neonatal onset
HP:0004319Decreased circulating aldosterone concentration
HP:0008221Adrenal hyperplasia
HP:0008872Feeding difficulties in infancy
HP:0008897Postnatal growth retardation
HP:0011410Caesarean section
HP:0011739Dexamethasone-suppressible primary hyperaldosteronism

GWAS associations

16 associations (top):

StudyTraitp-value
GCST004363_4Plasma androstenedione levels in resected early stage-receptor positive breast cancer7.000000e-07
GCST005979_15Systolic blood pressure4.000000e-12
GCST006010_12Mean arterial pressure9.000000e-11
GCST007094_188Diastolic blood pressure6.000000e-10
GCST007095_90Systolic blood pressure8.000000e-06
GCST007099_199Systolic blood pressure3.000000e-10
GCST007267_336Systolic blood pressure1.000000e-10
GCST007703_109Systolic blood pressure1.000000e-11
GCST007704_19Diastolic blood pressure3.000000e-09
GCST007705_1Pulse pressure7.000000e-06
GCST007706_31Mean arterial pressure1.000000e-11
GCST007706_54Mean arterial pressure1.000000e-11
GCST007707_31Hypertension2.000000e-08
GCST007707_60Hypertension3.000000e-08
GCST007928_81Medication use (diuretics)3.000000e-09
GCST011141_21Hypertension3.000000e-08

EFO canonical traits (6, from GWAS)

EFO IDTrait name
EFO:0007972androstenedione measurement
EFO:0006335systolic blood pressure
EFO:0006340mean arterial pressure
EFO:0006336diastolic blood pressure
EFO:0005763pulse pressure measurement
EFO:0009928Diuretic use measurement

MeSH disease descriptors (2)

DescriptorNameTree numbers
C563177Glucocorticoid-Remediable Aldosteronism (supp.)
C564638Hyperreninemic Hypoaldosteronism, Familial, 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2722 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

12 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 281,966 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL106FLUCONAZOLE458,942
CHEMBL1397POSACONAZOLE4541
CHEMBL1444LETROZOLE481,122
CHEMBL157101KETOCONAZOLE475,361
CHEMBL254328ABIRATERONE422,316
CHEMBL3099695OSILODROSTAT4347
CHEMBL681ETOMIDATE48,462
CHEMBL934METYRAPONE42,893
CHEMBL4113975BAXDROSTAT316
CHEMBL5095105LORUNDROSTAT335
CHEMBL287677DEXFADROSTAT2169
CHEMBL9298FADROZOLE231,762

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

2 annotations.

VariantTypeLevelDrugsPhenotypes
rs1799998Efficacy3benazepril;imidaprilEssential hypertension
rs1799998Efficacy3candesartanHypertension

PharmGKB variants

1 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs1799998CYP11B232.502benazepril;imidapril;candesartan

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — CYP11, CYP17, CYP19, CYP20 and CYP21 families

Most potent curated ligand interactions (7 total), top 7:

LigandActionAffinityParameter
osilodrostatInhibition9.7pIC50
fadrozoleInhibition9.1pKi
lorundrostatInhibition8.9pKi
dexfadrostatInhibition7.97pIC50
baxdrostatInhibition7.89pKi
vicadrostatInhibition7.8pIC50
metyraponeInhibition7.1pIC50

Binding affinities (BindingDB)

1017 measured of 1102 human assays (1102 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
(E)-2-(4-Chlorophenoxy)-3- (dimethylamino)-1-(2-methoxyphenyl)prop- 2-en-1-oneEC500.001 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
4-[(Z)-1-(2-Benzyloxybenzoyl)-2- (dimethylamino)vinyloxy]benzonitrileEC500.001 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
CHEM-US-00174EC500.003 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
CHEM-US-00182EC500.005 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
4-[[3-[2-(Pyridin-4-ylmethoxy)phenyl]-1H-pyrazol-4-yl]oxy]benzonitrileEC500.007 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
CHEM-US-00175EC500.007 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
CHEM-US-00172EC500.011 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
CHEM-US-00173EC500.011 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
4-[[3-(2-Fluoro-3-hydroxyphenyl)-1H-pyrazol-4-yl]oxy]benzonitrileEC500.017 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
(E)-1-[(2-Chlorobenzoyl)-2- (dimethylamino)vinyloxy]benzonitrileEC500.018 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
CHEM-US-00183EC500.028 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
Methyl 3-[(E)-2-(4-cyanophenoxy)- 3-(dimethylamino)prop-2-enoyl]benzoateEC500.031 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
CHEM-US-00129EC500.032 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
4-[[3-[3-[[3-Fluoro-3-(hydroxymethyl)azetidin-1-yl]methyl]phenyl]-1H-pyrazol-4-yl]oxy]benzonitrileEC500.036 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
CHEM-US-00162EC500.038 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
CHEM-US-00131EC500.046 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
4-[[3-[3-[(6-Fluoropyridin-2-yl)oxymethyl]phenyl]-1H-pyrazol-4-yl]oxy]benzonitrileEC500.048 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
(rac)-6-[4-[1-(1-Acetylpiperidin-4-yl)ethyl]-1H-pyrazol-3-yl]-5-fluoro-1-methyl-3,4-dihydroquinolin-2-oneEC500.049 nMUS-9796702: Dihydroquinoline pyrazolyl compounds
4-[3-[3-(pyridin-3-ylmethoxy)phenyl]pyrazolidin-4-yl]oxybenzonitrileEC500.051 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
(E)-2-(4-Chlorophenoxy)-1-(2- chlorophenyl)-3-(dimethylamino)prop-2-en- 1-oneEC500.052 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
4-[[3-[3-(Pyridin-2-ylmethoxy)phenyl]-1H-pyrazol-4-yl]oxy]benzonitrileEC500.052 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
4-[(Z)-1-(3-Benzyloxybenzoyl)-2- (dimethylamino)vinyloxy]benzonitrileEC500.053 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
(rac)-6-[4-[1-(1-Acetylpiperidin-4-yl)ethyl]-1H-pyrazol-3-yl]-7-fluoro-1-methyl-3,4-dihydroquinolin-2-oneEC500.067 nMUS-9796702: Dihydroquinoline pyrazolyl compounds
4-[(Z)-1-(2-Chloro-3-fluoro- benzoyl)- (dimethylamino)vinyloxy]benzonitrileEC500.069 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
(+)-6-[4-[(1R)-1-(1-acetylpiperidin-4-yl)ethyl]-1H-pyrazol-3-yl]-5-fluoro-1-methyl-3,4-dihydroquinolin-2-oneEC500.074 nMUS-9796702: Dihydroquinoline pyrazolyl compounds
(E)-2-(4-Chlorophenoxy)-1-[2- (difluoromethoxy)phenyl]-3- (dimethylamino)prop-2-en-1-oneEC500.076 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
CHEM-US-00074EC500.076 nMUS-9796702: Dihydroquinoline pyrazolyl compounds
4-[[3-(3-Hydroxyphenyl)-1H-pyrazol-4-yl]oxy]benzonitrileEC500.083 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
4-[[3-[3-(Hydroxymethyl)phenyl]-1H-pyrazol-4-yl]oxy]benzonitrileEC500.085 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
CHEM-US-00133EC500.094 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
1-methyl-6-[5-[(6-methyl-2-pyridinyl)sulfanylmethyl]-3-pyridinyl]-3,4-dihydroquinolin-2-oneEC500.1 nMUS-9458135: Dihydroquinoline-2-one derivatives
4-[[5-(3-Butoxyphenyl)-1H-pyrazol-4-yl]oxy]benzonitrileEC500.102 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
CHEM-US-00072EC500.133 nMUS-9796702: Dihydroquinoline pyrazolyl compounds
4-[(E)-1-(2-Chlorobenzoyl)-2- (dimethylamino)vinyloxy]-3-fluoro- benzonitrileEC500.134 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
4-[[3-[3-(Morpholin-4-ylmethyl)phenyl]-1H-pyrazol-4-yl]oxy]benzonitrileEC500.139 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
(rac)-4-[[3-[1-(1-Methylpyrazole-4-carbonyl)piperidin-3-yl]-1H-pyrazol-4-yl]oxy]benzonitrileEC500.15 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
(E)-2-(4-Chlorophenoxy)-1-(2,4- difluorophenyl)-3-(dimethylamino)prop-2- en-1-oneEC500.159 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
CHEM-US-00117EC500.159 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
(E)-1-[(2,3-Difluorobenzoyl)-2-(dimethylamino)vinyloxy]benzonitrileEC500.161 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
(E)-2-(4-Chlorophenoxy)-3- (dimethylamino)-1-(2-fluorophenyl)prop-2- en-1-oneEC500.167 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
CHEM-US-00176EC500.171 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
6-[4-[(1-Acetyl-4-piperidyl)methyl]-1H-pyrazol-3-yl]-5-fluoro-1-methyl-3,4-dihydroquinolin-2-oneEC500.184 nMUS-9796702: Dihydroquinoline pyrazolyl compounds
4-[(E)-1-(3-Chloro-2-fluoro- benzoyl)-2- (dimethylamino)vinyloxy]benzonitrileEC500.191 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
CHEM-US-00130EC500.198 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
(rac)-4-[[3-[3-(1-Acetylpyrrolidin-3-yl)oxyphenyl]-1H-pyrazol-4-yl]oxy]benzonitrileEC500.215 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
5-Chloro-6-[4-[(2-ethylsulfonyl-2-azaspiro[3.3]heptan-6-yl)methyl]-1H-pyrazol-3-yl]-1-methyl-3,4-dihydroquinolin-2-oneEC500.215 nMUS-9796702: Dihydroquinoline pyrazolyl compounds
6-[4-[(1-Ethylsulfonyl-4-piperidyl)methyl]-1H-pyrazol-3-yl]-1-methyl-3,4-dihydroquinolin-2-oneEC500.216 nMUS-9796702: Dihydroquinoline pyrazolyl compounds
(rac)-3-Fluoro-4-[[5-[1-(1-methylpyrazole-4-carbonyl)piperidin-3-yl]-1H-pyrazol-4-yl]oxy]benzonitrileEC500.231 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
(E)-1-(2-Chloro-3-fluoro-phenyl)-2- (4-chlorophenoxy)-3-(dimethylamino)prop-2- en-1-oneEC500.262 nMUS-9790217: Pyridinyloxy- and phenyloxy-pyrazolyl compounds
6-[4-[(1-Acetyl-4-piperidyl)methyl]-1H-pyrazol-3-yl]-1-methyl-3,4-dihydroquinolin-2-oneEC500.266 nMUS-9796702: Dihydroquinoline pyrazolyl compounds

ChEMBL bioactivities

3025 potent at pChembl≥5 of 3043 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
11.00EC500.01nMCHEMBL5794024
11.00EC500.01nMCHEMBL5955547
11.00EC500.01nMCHEMBL6056586
11.00EC500.01nMCHEMBL5993024
11.00EC500.01nMCHEMBL5806425
10.96EC500.011nMCHEMBL5846526
10.96EC500.011nMCHEMBL5754409
10.92EC500.012nMCHEMBL3916961
10.92EC500.012nMCHEMBL5849911
10.92EC500.012nMCHEMBL5767596
10.92EC500.012nMCHEMBL5877749
10.89EC500.013nMCHEMBL5789906
10.85EC500.014nMCHEMBL4632981
10.85EC500.014nMCHEMBL5960934
10.82EC500.015nMCHEMBL5935291
10.82EC500.015nMCHEMBL5901252
10.82EC500.015nMCHEMBL5965994
10.82EC500.015nMCHEMBL5870745
10.80EC500.016nMCHEMBL5760532
10.77EC500.017nMCHEMBL5928932
10.77EC500.017nMCHEMBL5949511
10.77EC500.017nMCHEMBL5848123
10.74EC500.018nMCHEMBL5965425
10.74EC500.018nMCHEMBL6020579
10.72EC500.019nMCHEMBL5947135
10.72EC500.019nMCHEMBL5971655
10.72EC500.019nMCHEMBL5840628
10.70EC500.02nMCHEMBL5930370
10.70EC500.02nMCHEMBL5876457
10.70EC500.02nMCHEMBL5816213
10.68EC500.021nMCHEMBL5817118
10.62EC500.024nMCHEMBL5755111
10.62EC500.024nMCHEMBL5858242
10.62EC500.024nMCHEMBL5979599
10.60EC500.025nMCHEMBL5811264
10.60EC500.025nMCHEMBL5778806
10.59EC500.026nMCHEMBL5878312
10.57EC500.027nMCHEMBL5993382
10.57EC500.027nMCHEMBL5850242
10.55EC500.028nMCHEMBL5844639
10.55EC500.028nMCHEMBL5840143
10.55EC500.028nMCHEMBL6039670
10.55EC500.028nMCHEMBL5919201
10.54EC500.029nMCHEMBL5843772
10.52EC500.03nMCHEMBL5882012
10.52EC500.03nMCHEMBL6062016
10.49EC500.032nMCHEMBL5844431
10.48EC500.033nMCHEMBL5918071
10.47EC500.034nMCHEMBL5935643
10.42EC500.038nMCHEMBL5899256

PubChem BioAssay actives

1440 with measured affinity, of 1939 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
6-isoquinolin-4-yl-1-methyl-3,4-dihydroquinolin-2-one389805: Inhibition of human CYP11B2 expressed in hamster V79 MZh cellsic500.0001uM
Etomidate553066: Inhibition of human CYP11B2 expressed in hamster V79MZ cells using 11-deoxycorticosterone substrateic500.0001uM
4-(6,7-difluoro-1-methylbenzimidazol-2-yl)isoquinoline1177651: Inhibition of human aldosterone synthase expressed in V79 MZ cellsic500.0001uM
5-chloro-2-[5-[2-(1-ethylpyrazole-4-carbonyl)-2,6-diazaspiro[3.3]heptan-6-yl]-3-pyridinyl]-3,3-dimethylisoindol-1-one2109202: Inhibition of human CYP11B2 stably expressed in G-402 cellsic500.0002uM
3-(methoxymethyl)-5-(6-methoxynaphthalen-2-yl)pyridine362124: Inhibition of human CYP11B2 expressed in hamster V79 MZh cellsic500.0002uM
3-(1-methoxyethyl)-5-(6-methoxynaphthalen-2-yl)pyridine362124: Inhibition of human CYP11B2 expressed in hamster V79 MZh cellsic500.0002uM
6-isoquinolin-4-yl-3,4-dihydro-1H-quinolin-2-one389805: Inhibition of human CYP11B2 expressed in hamster V79 MZh cellsic500.0002uM
6-(5-methoxy-3-pyridinyl)-1-methyl-3,4-dihydroquinolin-2-one389805: Inhibition of human CYP11B2 expressed in hamster V79 MZh cellsic500.0002uM
Osilodrostat1154696: Inhibition of CYP11B2 (unknown origin)ic500.0002uM
6-isoquinolin-4-yl-1-azatricyclo[6.3.1.04,12]dodeca-4,6,8(12)-trien-11-one592041: Inhibition of human CYP11B2 expressed in hamster V79 MZh cells assessed as conversion of [4-14C]-11-deoxycorticosterone substrate by HPTLC assayic500.0002uM
7-isoquinolin-4-yl-1-azatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-2-one592041: Inhibition of human CYP11B2 expressed in hamster V79 MZh cells assessed as conversion of [4-14C]-11-deoxycorticosterone substrate by HPTLC assayic500.0002uM
1-cyclopropyl-2-(4,5-dimethyl-3-pyridinyl)-5,6-difluorobenzimidazole1229390: Inhibition of human CYP11B2 expressed in V79 cells incubated for 1 hr before 11-deoxycorticosterone substrate addition by HTRF-based assayic500.0002uM
2-[5-(4-chloro-7-fluoroindazol-1-yl)-3-pyridinyl]propan-2-ol1474789: Inhibition of human CYP11B2-CLE9 expressed in Chinese hamster V79 cells using 11-deoxycorticosterone as substrate preincubated for 1 hr followed by substrate addition measured for 3 hrs by HTRF assayic500.0002uM
2-fluoro-4-[5-(2-methyl-1,3-dioxolan-2-yl)-3-pyridinyl]benzonitrile1977386: Inhibition of human CYP11B2 stably transfected in mouse Y-1 cells using deoxycortisol or deoxycorticosterone as substrate incubated for 48 hrs by radioimmuno assayic500.0003uM
2-[5-(4,7-difluoroindazol-1-yl)-3-pyridinyl]propan-2-ol1474789: Inhibition of human CYP11B2-CLE9 expressed in Chinese hamster V79 cells using 11-deoxycorticosterone as substrate preincubated for 1 hr followed by substrate addition measured for 3 hrs by HTRF assayic500.0003uM
6-isoquinolin-4-yl-1,4-dihydro-3,1-benzoxazin-2-one1191378: Inhibition of CYP11B2 in human V79MZ cells using [3H]-11-deoxycorticosterone as substrate incubated for 1 hr prior to substrate addition measured after 45 mins by HPLC analysisic500.0003uM
(1S)-2-[2-[(1S)-1-(4-chlorophenyl)ethyl]-3,3-dioxo-1,4-dihydroimidazo[5,1-d][1,2,5]thiadiazin-4-yl]-1-phenylethanol493924: Inhibition of human recombinant CYP11B2 by cell-based assayic500.0003uM
2-[5-(1-cyclopropyl-5,6-difluorobenzimidazol-2-yl)-3-pyridinyl]propan-2-ol1229390: Inhibition of human CYP11B2 expressed in V79 cells incubated for 1 hr before 11-deoxycorticosterone substrate addition by HTRF-based assayic500.0003uM
[4-(4-fluorophenyl)sulfanylpyrimidin-5-yl]-(1-methylsulfonylpiperidin-4-yl)methanol1444794: Inhibition of human CYP11B2 expressed in HEK293A cells using deoxycorticosterone as substrate pretreated for 1 hr followed by substrate addition measured after 1 hr by HTRF assayic500.0004uM
6-chloro-1-cyclopropyl-5-fluoro-2-pyridin-3-ylbenzimidazole1229390: Inhibition of human CYP11B2 expressed in V79 cells incubated for 1 hr before 11-deoxycorticosterone substrate addition by HTRF-based assayic500.0004uM
1-cyclopropyl-5,6-difluoro-2-(5-methoxy-3-pyridinyl)benzimidazole1229390: Inhibition of human CYP11B2 expressed in V79 cells incubated for 1 hr before 11-deoxycorticosterone substrate addition by HTRF-based assayic500.0004uM
3-(4-fluorophenyl)-4-[(5R)-6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepin-5-yl]benzonitrile1059816: Inhibition of human recombinant CYP11B2 using 11-deoxycorticosterone as substrate by cell-based assayic500.0004uM
5-chloro-3,3-dimethyl-2-[5-[1-(1-methylpyrazole-4-carbonyl)azetidin-3-yl]oxy-3-pyridinyl]isoindol-1-one1658216: Inhibition of human CYP11B2 expressed in human renal leiomyoblastoma cells harboring FDXR/FDX using 1-deoxycorticosterone as substrate by HTRF assayic500.0005uM
1-[5-(6-methoxynaphthalen-2-yl)-3-pyridinyl]ethanol362124: Inhibition of human CYP11B2 expressed in hamster V79 MZh cellsic500.0005uM
4-(6-methoxy-3-methyl-3,4-dihydronaphthalen-2-yl)isoquinoline2109203: Inhibition of human CYP11B2 expressed in human NCI-H295 cells incubated for 48 hrs by radioimmuno assayic500.0005uM
7-isoquinolin-4-yl-4H-1,4-benzoxazin-3-one1191378: Inhibition of CYP11B2 in human V79MZ cells using [3H]-11-deoxycorticosterone as substrate incubated for 1 hr prior to substrate addition measured after 45 mins by HPLC analysisic500.0005uM
1-cyclopropyl-5,6-difluoro-2-(5-fluoro-4-methyl-3-pyridinyl)benzimidazole1229390: Inhibition of human CYP11B2 expressed in V79 cells incubated for 1 hr before 11-deoxycorticosterone substrate addition by HTRF-based assayic500.0005uM
2-phenyl-5-[(5-phenyl-3-pyridinyl)methyl]pyridine765521: Inhibition of human CYP11B2 expressed in hamster V79MZh cells using [1,2-3H]-11-deoxycorticosterone as substrateic500.0005uM
3-cyclopropyl-6-fluoro-2-pyridin-3-ylbenzimidazole-5-carbonitrile1229390: Inhibition of human CYP11B2 expressed in V79 cells incubated for 1 hr before 11-deoxycorticosterone substrate addition by HTRF-based assayic500.0006uM
N-(4-fluorophenyl)-5-(1-methylsulfonylpiperidin-4-yl)sulfanylpyrimidin-4-amine2109497: Inhibition of human CYP11B2 expressed in HEK293-A cells harboring FDXR/FDX using deoxycorticosterone as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hric500.0006uM
4-(6-methoxynaphthalen-2-yl)isoquinoline362124: Inhibition of human CYP11B2 expressed in hamster V79 MZh cellsic500.0006uM
6-(4-methyl-3-pyridinyl)naphthalene-2-carbonitrile362124: Inhibition of human CYP11B2 expressed in hamster V79 MZh cellsic500.0006uM
6-(5-methoxy-3-pyridinyl)-1-azatricyclo[6.3.1.04,12]dodeca-4,6,8(12)-trien-11-one592041: Inhibition of human CYP11B2 expressed in hamster V79 MZh cells assessed as conversion of [4-14C]-11-deoxycorticosterone substrate by HPTLC assayic500.0006uM
1-cyclopropyl-5,6-difluoro-2-(4-methoxy-5-methyl-3-pyridinyl)benzimidazole1229390: Inhibition of human CYP11B2 expressed in V79 cells incubated for 1 hr before 11-deoxycorticosterone substrate addition by HTRF-based assayic500.0006uM
4-(3-cyclopropyl-6-fluoroimidazo[1,2-a]pyridin-2-yl)isoquinoline1332279: Inhibition of human CYP11B2-CLE9 expressed in Chinese hamster V79 cells using 11-deoxycorticosterone as substrate preincubated for 1 hr followed by substrate addition measured after 3 hrs by HTRF assayic500.0006uM
1-(5-isoquinolin-4-ylindol-1-yl)ethanone1154700: Inhibition of human CYP11B2 expressed in hamster V79MZh cells using deoxycorticosterone as substrateic500.0006uM
2,2,2-trifluoro-1-[4-(4-fluoroanilino)pyrimidin-5-yl]-1-(1-methylsulfonylpiperidin-4-yl)ethanol1444794: Inhibition of human CYP11B2 expressed in HEK293A cells using deoxycorticosterone as substrate pretreated for 1 hr followed by substrate addition measured after 1 hr by HTRF assayic500.0007uM
6-[5-(2-fluorophenyl)-3-pyridinyl]-1-azatricyclo[6.3.1.04,12]dodeca-4,6,8(12)-trien-11-one592041: Inhibition of human CYP11B2 expressed in hamster V79 MZh cells assessed as conversion of [4-14C]-11-deoxycorticosterone substrate by HPTLC assayic500.0007uM
1-(5-isoquinolin-4-yl-2,3-dihydroindol-1-yl)ethanone1154700: Inhibition of human CYP11B2 expressed in hamster V79MZh cells using deoxycorticosterone as substrateic500.0007uM
4-[6-(diethylamino)pyrazin-2-yl]-2-fluorobenzonitrile1977386: Inhibition of human CYP11B2 stably transfected in mouse Y-1 cells using deoxycortisol or deoxycorticosterone as substrate incubated for 48 hrs by radioimmuno assayic500.0008uM
N-(4-fluorophenyl)-5-(1-methylsulfonylpiperidin-4-yl)sulfonylpyrimidin-4-amine2109497: Inhibition of human CYP11B2 expressed in HEK293-A cells harboring FDXR/FDX using deoxycorticosterone as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hric500.0008uM
methyl 5-(6-methoxynaphthalen-2-yl)pyridine-3-carboxylate362124: Inhibition of human CYP11B2 expressed in hamster V79 MZh cellsic500.0008uM
3-(6-methoxynaphthalen-2-yl)-4-methylpyridine362124: Inhibition of human CYP11B2 expressed in hamster V79 MZh cellsic500.0008uM
2-[(1S)-1-(4-chlorophenyl)ethyl]-4-(propan-2-yloxymethyl)-1,4-dihydroimidazo[5,1-d][1,2,5]thiadiazine 3,3-dioxide493924: Inhibition of human recombinant CYP11B2 by cell-based assayic500.0008uM
6-chloro-1-cyclopropyl-5-fluoro-2-(5-fluoro-3-pyridinyl)benzimidazole1229390: Inhibition of human CYP11B2 expressed in V79 cells incubated for 1 hr before 11-deoxycorticosterone substrate addition by HTRF-based assayic500.0008uM
4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)benzonitrile1154700: Inhibition of human CYP11B2 expressed in hamster V79MZh cells using deoxycorticosterone as substrateic500.0008uM
4-[6-(dimethylamino)pyrazin-2-yl]-2-fluorobenzonitrile1977386: Inhibition of human CYP11B2 stably transfected in mouse Y-1 cells using deoxycortisol or deoxycorticosterone as substrate incubated for 48 hrs by radioimmuno assayic500.0009uM
2-fluoro-4-[5-(4-methyl-1,3-dioxolan-2-yl)-3-pyridinyl]benzonitrile1977386: Inhibition of human CYP11B2 stably transfected in mouse Y-1 cells using deoxycortisol or deoxycorticosterone as substrate incubated for 48 hrs by radioimmuno assayic500.0009uM
N-(4-fluorophenyl)-5-(4-methylsulfonylpiperazin-1-yl)sulfonylpyrimidin-4-amine2109497: Inhibition of human CYP11B2 expressed in HEK293-A cells harboring FDXR/FDX using deoxycorticosterone as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hric500.0009uM
7-(5-methoxy-3-pyridinyl)-1-azatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-2-one592041: Inhibition of human CYP11B2 expressed in hamster V79 MZh cells assessed as conversion of [4-14C]-11-deoxycorticosterone substrate by HPTLC assayic500.0009uM

CTD chemical–gene interactions

109 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
Colforsindecreases expression, increases expression, decreases reaction, increases reaction, affects cotreatment (+1 more)10
3,4,5,3’,4’-pentachlorobiphenylincreases activity, increases expression, increases reaction, affects cotreatment6
Aldosteroneincreases chemical synthesis, increases hydroxylation, affects chemical synthesis5
torcetrapibincreases expression, decreases reaction4
Fadrozoledecreases activity4
Flame Retardantsincreases expression, decreases expression3
Ketoconazoleaffects binding, decreases activity, increases expression, increases reaction3
tributyltinaffects cotreatment, increases expression2
2,4,5,2’,4’,5’-hexachlorobiphenylincreases expression, affects cotreatment2
perfluorooctane sulfonic acidincreases expression, affects cotreatment2
2,2’,4,4’-tetrabromodiphenyl etherincreases expression, affects cotreatment2
Benzo(a)pyreneaffects methylation, increases expression2
Corticosteroneaffects metabolic processing, increases chemical synthesis, increases hydroxylation2
Cortodoxoneaffects metabolic processing, increases metabolic processing2
Desoxycorticosteroneincreases chemical synthesis, affects metabolic processing, increases hydroxylation2
Potassiumincreases expression, decreases reaction2
Valproic Acidincreases expression, increases methylation2
8-Bromo Cyclic Adenosine Monophosphateincreases expression2
Halogenated Diphenyl Ethersdecreases expression, increases expression2
fluorene-9-bisphenolaffects reaction, increases expression, decreases expression1
triptolidedecreases expression, affects cotreatment1
perflubronincreases expression1
2,4,6-tribromophenoldecreases expression1
methylmercuric chlorideincreases expression, affects cotreatment1
alternariolincreases expression1
naringindecreases reaction, increases expression1
bisphenol Adecreases expression1
deoxynivalenolincreases expression1
4,4’-bisphenol Fdecreases expression1
2,4,5,2’,5’-pentachlorobiphenylincreases expression1

ChEMBL screening assays

147 unique, capped per target: 135 binding, 12 admet

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1002226BindingInhibition of human CYP11B2 expressed in hamster V79 MZh cellsOvercoming undesirable CYP1A2 inhibition of pyridylnaphthalene-type aldosterone synthase inhibitors: influence of heteroaryl derivatization on potency and selectivity. — J Med Chem
CHEMBL2433420ADMETInhibition of human CYP11B2Emerging technologies for metabolite generation and structural diversification. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_4710V79MZh11B2Spontaneously immortalized cell lineMale

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.